CP-091 SLC9A7 G/T (RS7055107) genetic polymorphism on the response to tocilizumab in rheumatoid arthritis patients


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Abstract

BackgroundThe SLC9A7 gene encodes a sodium and potassium proton antiporter (NHE7). This protein is localised in the trans-Golgi network, involved in protein transport for glycoprotein production. Interleukin 6 (IL-6) is a multifunctional glycoprotein involved in the immune response, and inflammation and bone metabolism; IL-6 makes significant contributions to autoimmune and inflammatory diseases such as rheumatoid arthritis (RA). Tocilizumab is a humanised monoclonal antibody inhibitor of IL-6 receptor, indicated in combination with methotrexate in the treatment of RA patients with inadequate response or intolerance to previous therapies.PurposeThe aim of this study was evaluate the role of the SLC9A7 G/T (rs7055107) genetic polymorphism on the response to tocilizumab in RA patients.Material and methodsThe SLC9A7 G/T (rs7055107) genetic polymorphism was genotyped using predesigned TaqMan genotyping assay technology and analysed on a ViiA7 real time PCR system. Clinical response was evaluated at 6 and 12 months after the first infusion of the drug with the use of the 28 joint disease activity score criteria (DAS28). Remission was classified according to EULAR criteria. EULAR remission was defined as achieving DAS28 ≤2.6. Statistical analysis was performed using SPSS V.20.ResultsClinical data from 140 tocilizumab treated patients were obtained. Patients were aged (mean±SD) 53.25±12.42 years and 79% were women. Mean DAS28 at baseline was 5.71±1.13. The SLC9A7 G/T polymorphism was significantly associated with remission according to EULAR criteria at 6 months (GG vs no-GG p=0.04; OR 0.42; 95% CI 0.18–0.99) and almost at 12 months (GG vs no-GG p=0.053; OR 0.46; 95% CI 0.21–1.01).ConclusionOur results showed that the SLC9A7 G/T (rs7055107) polymorphisms can be useful as a genetic marker of tocilizumab efficacy in RA patients. More studies are necessary to confirm these results.No conflict of interest

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